17-8288435-G-GTCAA

Position:

• chr17-8288435-G-GTCAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000579192.5(SLC25A35):​c.*43-4_*43-3insTTGA variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 377,794 control chromosomes in the GnomAD database, including 188 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (84 hom., cov: 31)
  • Exomes 𝑓: 0.028 (104 hom.)
• Consequence: SLC25A35 ENST00000579192.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.138

Genes affected

SLC25A35 (HGNC:31921): (solute carrier family 25 member 35) SLC25A35 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-8288435-G-GTCAA is Benign according to our data. Variant chr17-8288435-G-GTCAA is described in ClinVar as [Likely_benign]. Clinvar id is 1317732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0302 (4586/151892) while in subpopulation NFE AF= 0.0435 (2956/67910). AF 95% confidence interval is 0.0422. There are 84 homozygotes in gnomad4. There are 2135 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 84 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A35	NM_201520.3	c.*1180_*1181insTTGA		3_prime_UTR_variant	6/6		NP_958928.1
SLC25A35	XM_047435999.1	c.*1478_*1479insTTGA		3_prime_UTR_variant	6/6		XP_047291955.1
SLC25A35	XM_047436000.1	c.*1478_*1479insTTGA		3_prime_UTR_variant	6/6		XP_047291956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A35	ENST00000579192.5	c.*43-4_*43-3insTTGA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000462395
SLC25A35	ENST00000380067.6	c.*1180_*1181insTTGA		3_prime_UTR_variant	6/6	2		ENSP00000369407
SLC25A35	ENST00000581320.1	n.91-4_91-3insTTGA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4583 AN: 151772 Hom.: 84 Cov.: 31

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0716

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.0312

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0138

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.0336

GnomAD4 exome AF: 0.0279 AC: 6307 AN: 225902 Hom.: 104 Cov.: 0 AF XY: 0.0266 AC XY: 3246 AN XY: 121908

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.000461

Gnomad4 SAS exome AF: 0.0148

Gnomad4 FIN exome AF: 0.0269

Gnomad4 NFE exome AF: 0.0363

Gnomad4 OTH exome AF: 0.0283

GnomAD4 genome AF: 0.0302 AC: 4586 AN: 151892 Hom.: 84 Cov.: 31 AF XY: 0.0287 AC XY: 2135 AN XY: 74270

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0246

Gnomad4 ASJ AF: 0.0312

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0142

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.0435

Gnomad4 OTH AF: 0.0332

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs138372313; hg19: chr17-8191753;